Compositions for Balancing Gut Microbiota and the Preparation and the Uses thereof

ABSTRACT

A composition includes a first composition, a second composition and a third composition. The first composition comprises edible ingredients from fruit, seeds, or other parts of plants; the second composition comprises bitter gourd, a first oligosaccharides, a first fermentable dietary fiber, or a combination thereof; and the third composition comprises a second oligosaccharides and a second fermentable dietary fiber. The composition is used for targeting and restoring structural balance of gut microbiota and relieving chronic inflammation.

TECHNICAL FIELD

The present application relates to compositions for promoting health.More specifically, the application provides compositions for promotingbeneficial gut microbiota or inhibiting opportunistic pathogens, as wellas the preparation and use of the composition.

BACKGROUND

Unless otherwise indicated herein, the materials described in thissection are not prior art to the claims in this application and are notadmitted to be prior art by inclusion in this section. All referencesare incorporated herein in their entirety.

Metabolic syndrome is characterized by, among others, hyperglycemia,hypertension, high cholesterol and overweight. Its most importantfeatures are central obesity and insulin resistance. Metabolic syndromeis a high-risk predisposing factor for many chronic diseases such asdiabetes, coronary heart disease, cerebral apoplexy and colon cancer,making the metabolic syndrome one of the major health threats. Thedevelopment of new technologies and methods for treating metabolicsyndrome is of vital importance to public health.

Currently, control of metabolic syndrome is mainly through use of drugsand changing the composition of diet. For a long while, because there isno breakthrough in understanding the causes of metabolic syndrome, theuse of drugs has been limited to addressing the symptoms instead of thecause of metabolic syndrome. Although the symptoms may be relieved,disease processes are not blocked, and most patients still developdifferent chronic diseases. Attempts to address metabolic syndrome bychanging diet composition does not fare better, because the past effortsgenerally emphasize the role of a particular nutrient while ignoring theunderlying cause of metabolic syndrome. For example, various iterationsof low-sugar food to control blood sugar or low-fat food to controlblood lipids are popular mainstay, yet success is uncommon, improvementis limited, because the underlying cause of metabolic syndrome is notproperly addressed. If diet composition is changed substantially, suchas when shifting from high-calorie food of animal origin to plant-basedfood, or drastic reduction of calorie intake, patients tend to sufferfrom various adverse reactions, such as unbearable food craving orincreased level of inflammatory response, resulting in the failure tostrictly follow medical guidance in long term.

SUMMARY

The following summary is illustrative only and is not intended to be inany way limiting. In addition to the illustrative aspects, embodiments,and features described above, further aspects, embodiments, and featureswill become apparent by reference to the drawings and the followingdetailed description.

The present application relates to an unexpected discovery that a newcomposition is effective in promoting beneficial intestinal bacteriawhile inhibiting opportunistic pathogens, resulting in prevention and/ortreatment of metabolic syndrome.

In one aspect, the application provides compositions for improving gutmicrobiota population. In one embodiment, the composition includes afirst composition, a second composition and a third composition. Thefirst composition may include an ingredient from an edible plant. Thesecond composition may include bitter gourd, a first fermentable dietaryfiber and a first oligosaccharide; and the third composition may includea second fermentable dietary fiber and a second oligosaccharide. Thefirst and the second fermentable dietary fiber may or may not be thesame. The first and the second oligosaccharide may or may not be thesame.

The ingredients in the compositions listed above may include seeds,fruits or other parts or their extracts of a plant that is edible andknown or recognized to have medicinal or therapeutic activities.

When ingested by a subject in effective amount, the composition may becapable of increasing a first gut microbiota population includingpopulation a short-chain fatty acid (SCFA)-producing bacteria,decreasing a second gut microbiota population including an endotoxinproducing bacteria in the subject, or both. For example, the firstcomposition may be capable of increasing the first gut microbiotapopulation, and the second composition may be capable of decreasing thesecond gut microbiota population in the subject.

The compositions in this application may be food, nutriceuticalproducts, supplements, or healthcare products. The composition may beadministered orally to a subject in need thereof. The subject may be ahuman being. The subject may suffer from metabolic syndrome.

In another aspect, this application provides methods for making theabove compositions. In one embodiment, the method includes mixing adlay,oat, buckwheat, white bean, yellow corn, red bean, soybean, yam, bigjujube, peanut, lotus seed, and wolfberry to provide a firstcomposition; mixing bitter gourd, a first fermentable dietary fiber anda first oligosaccharides to provide a second composition; and mixing asecond fermentable dietary fiber and a second oligosaccharides toprovide a third composition.

In a third aspect, the application provides methods for balancing gutmicrobiota and/or improving metabolic syndrome in a subject. In oneembodiment, the method includes the steps of administering to thesubject an effective amount of a treatment composition. The treatmentcomposition may include the above described first composition, the abovedescribed second composition, the above described third composition, orany combination of the three compositions.

Compared to existing techniques, the solutions in the presentapplication have, among others, one or more following surprisingadvantages: when administered to the subject, the compositions arecapable of balancing or improve gut microbiota in a subject, improvingmetabolic syndrome, increasing the amount of short-chain fattyacid-producing bacteria and decreasing the amount of endotoxin-producingbacteria; the compositions may be administered to a subject via variousforms and may alleviate, relieve, remedy, prevent or amelioratemetabolic syndrome or symptoms of metabolic syndrome and/or restorehealth to the subject.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other features of this disclosure will become morefully apparent from the following description and appended claims, takenin conjunction with the accompanying drawings. Understanding that thesedrawings depict only several embodiments arranged in accordance with thedisclosure and are, therefore, not to be considered limiting of itsscope, the disclosure will be described with additional specificity anddetail through use of the accompanying drawings, in which:

FIG. 1 shows the fingerprints of the 16S rRNA gene V3-DGGE of the gutmicrobiota population from the volunteers before and after theintervention.

DETAILED DESCRIPTION

In the following detailed description, reference is made to theaccompanying drawings, which form a part hereof. In the drawings,similar symbols typically identify similar components, unless contextdictates otherwise. The illustrative embodiments described in thedetailed description, drawings, and claims are not meant to be limiting.Other embodiments may be utilized, and other changes may be made,without departing from the spirit or scope of the subject matterpresented herein. It will be readily understood that the aspects of thepresent disclosure, as generally described herein, and illustrated inthe Figures, can be arranged, substituted, combined, separated, anddesigned in a wide variety of different configurations, all of which areexplicitly contemplated herein.

In one aspect, the application provides novel compositions that areeffective in promoting the beneficial gut microbiota population orinhibiting the opportunistic pathogens. The composition may be anutritional intervention composition. The composition may be made fromcommon food ingredients and may not contain any artificial syntheticcolors, hormones, sweeteners, flavoring agents, preservatives, or anyillicit drugs, thus is safe and nontoxic. The composition overcomes theinsufficiency of the existing nutritional intervention methods fortreating metabolic syndrome, and is effective in inhibiting intestinalopportunistic pathogens, increasing the number of beneficial bacteria,reducing chronic inflammation, thus fundamentally improving metabolicsyndrome symptoms.

In one embodiment, the composition includes a first composition, asecond composition and a third composition. In one embodiment, the firstcomposition comprises an ingredient from an edible plant. The secondcomposition may contain bitter gourd, a first fermentable dietary fiberand a first oligosaccharide; and the third composition contains a secondfermentable dietary fiber and a second oligosaccharide.

The first composition may be capable of increasing short-chain fattyacid (SCFA)-producing bacteria population in a subject. In oneembodiment, the first composition may include whole cereals, beans,nuts, peanuts, corn (including, for example, yellow corn, white corn,red corn, purple corn, black corn, bi-color corn, multi-color corn),cloves, star anise, fennel, thistle, yam, hawthorn, purslane, Zaocysdhumnades, plum, papaya, hemp seed, odoratum, fragrant Solomonsealrhizome, licorice, angelica, ginkgo, white lentils, white lentilsflower, longan pulp (also called Gui Yuan), cassia, lily, nutmeg,cinnamon, amla, bergamot, almond (either sweet or bitter), Hippophaerhamnoides, oysters, Gorgon fruit, pepper, red beans, donkey hidegelatin, inner wall of chicken gizzard, malt, kelp, jujube (including,for example, Zizyphus jujube, sour jujube, or black jujube), Momordicagrosvenori, Yu Li seed, honeysuckle flower, olive, Houttuynia cordata,ginger (including, for example, Zingiber officinale, fresh or dried),Hovenia dulcis Thunb, medlar, gardenia, Amomum villosum, Pang Dahai,Poria, citron, Elsholtzia, peach kernel, mulberry leaf, mulberry,orange, bellflower, Alpinia oxyphylla, lotus leaf, semen raphani, lotusseed, Alpinia officinarum hance, Lophatherum gracile, fermented soybean,chrysanthemum, chicory, Huang Jiezi, Huang Jing, perilla seed, perillaseed, Ge Gen, black sesame seed, black pepper, Sophora japonica, sophoraflower, dandelion, honey, Torreya, semen Ziziphi Spinosae, Rhizomaimperatae, reed rhizome, viper, orange peel, adlay (also known as coixseed or Yi Ren), peppermint, Allium macrostemon Bunge, raspberry,ageratum, or any combination thereof.

The beans may include soybeans, black beans, broad beans, white beans,peas, mung bean, long bean, Pigeonpea, four winged bean, chickpea,lentil, red beans, Pinto bean, green bean, kidney bean, Navy bean, Peabean, Lima bean, black bean, Garbanzo peas, black-eyed peas, lablab beanor any combination thereof. In one embodiment, the lablab bean mayinclude white Hyacinth bean and white Hyacinth flowers. In oneembodiment, the lablab bean may include bean from a plant of Hyacinthus.

The nuts may include peach seeds, almonds, gingko seeds, or acombination thereof. In one embodiment, the almonds may include sweetalmonds or bitter almonds.

The whole cereals may include rice, wheat, barley, quinoa, rye,triticale, buckwheat, or oat. The buckwheat may include commonbuckwheat, bitter Tartary buckwheat, or a combination thereof. In oneembodiment, the buckwheat may include seeds from a plant of Gagopyrum,Erigonum, or Fallopia. The oat may include seeds from a plant of Avena.

In one embodiment, the first composition may include powder or granularparticles of the whole cereals. In one embodiment, from about 15 toabout 100% of the whole cereal granular particles have a diameter of0.65 mm or above. In some embodiments, at least about 15%, at leastabout 20%, at least about 25%, at least about 30% or at least about 50%of the granular particles of the whole cereals have diameter of 0.65 mmor above.

In one embodiment, the first composition may include buckwheat, oats,adlay, or a combination of any two, three, four, five, or sixingredients selected from the group. In another embodiment, the firstcomposition may include oats, white Hyacinth bean, adlay or acombination of any two, three, four, five, or six ingredients selectedfrom the group. In another embodiment, the first composition includesbuckwheat, oat, yam or any combination of two, three, four, five, or sixingredients selected from the group. For example, the first compositionincludes from about 10 to about 30% of adlay by weight, from about 5 toabout 30% of oat by weight, from about 5 to about 50% of buckwheat byweight, from about 5 to about 20% of white Hyacinth bean by weight, fromabout 5 to about 30% of yam by weight, or any combination thereof. Inone embodiment, the yam is dried yam.

In one embodiment, the first composition may include adlay, oat,buckwheat, white bean, yellow corn, red bean, soybean, yam, peanut,lotus seed, and wolfberry. For example, the first composition includesabout 20% by weight of adlay, about 15% by weight of oat, about 10% byweight of buckwheat, about 10% by weight of white Hyacinth beans, about5% by weight of yellow corn, about 5% by weight of red bean, about 5% byweight of soybean, about 10% by weight of dried yam, about 5% by weightof big jujube, about 5% by weight of peanut, about 5% by weight of lotusseed, and about 5% by weight of wolfberry.

In one embodiment, the first composition may include adlay, oat,buckwheat, lablab bean, yellow corn, red bean, soybean (or soy protein),yam, big jujube, peanut, lotus seed, and wolfberry. For example, theamount of the adlay may be from about 10 to about 30%, such as about10%, about 15%, about 20%, about 25%, or about 30%, by weight of thefirst composition. The amount of the oat may be from about 5 to about25%, such as about 5%, about 10%, 15%, 20%, or 25%, by weight of thefirst composition. The buckwheat may be from about 1 to about 20%, suchas about 1%, 5%, about 10%, about 15%, or about 20%, by weight of thefirst composition. The amount of the lablab bean may be from about 1 toabout 20%, such as about 1%, about 5%, about 10%, about 15%, or about20%, by weight of the first composition. The amount of the yam may befrom about 1 to about 20%, such as about 1%, about 5%, about 10%, about15%, or about 20%, by weight of the first composition. In someembodiments, the yam may be in dried, frozen, canned, or in extractedform. The amount of wolfberry may be from about 5 to about 25%, suchabout 5%, about 10%, about 15%, about 20%, or about 25%, of the firstcomposition by weight. The amount of soybean may be from about 1 toabout 20%, such as about 1%, about 5%, about 10%, about 15%, or about20%, of the first composition by weight.

In one embodiment, the amount of the adlay, oat, buckwheat, white bean,and yam in the first composition may be about 20%, about 15%, about 10%,about 10%, and 10% by weight, respectively, of the first composition,and the amount of each of the yellow corn, red bean, soybean, bigjujube, peanut, lotus seed, and wolfberry may be about 5% by weight ofthe first composition.

In one embodiment, the first composition may include, per 100 g, VitaminA from about 3 to about 857 μgRE, Vitamin D from about 0.01 to about 5μgRE, Vitamin E from about 2 to about 79.09 mg, Vitamin Bi from about0.01 to about 1.89 mg, Vitamin B2 from about 0.01 mg to about 1.4 mg,Vitamin B₆ from about 0.01 to about 1.2 mg, Vitamin B12 from about 0.1to about 2.4 mg, Vitamin C from about 1 mg to about 1170 mg, Niacin fromabout 0.5 mgNE to about 28.4 mg, calcium (Ca) from about 60-2458 mg,phosphorus (P) from about 200 to about 1893 mg, potassium (K) from about350 to about 1796 mg, sodium (Na) from about 8 to about 2200 mg,magnesium (Mg) from about 100 to about 350 mg, and iron (Fe) from about2 to about 20 mg.

In one embodiment, the first composition includes from about 5 to about40% or from about 10 to about 20% of protein by weight, from about 30 toabout 80% or from about 50 to about 70% of carbohydrate by weight, fromabout 0.5 to about 30% or from about 2 to about 15% of fat by weight,from about 0.5 to about 30% or from about 2 to about 15% of dietaryfiber by weight, from about 0.1 to about 5% or from about 0.5 to about1% of vitamin(s) by weight, or from about 0.1 to about 2% or from about0.8 to about 1.2% of mineral(s) by weight.

In one embodiment, every 100 grams of the first composition may providea total of from about 300 to about 400 calories. In one embodiment, theamount of protein, carbohydrate, fat, fiber, vitamin, and mineral may befrom about 13 to about 15%, from about 60 to about 65%, from about 4 toabout 6%, from about 5 to about 7%, from about 0.5 to about 1%, and fromabout 0.8 to about 1.2% by weight, respectively, of the firstcomposition.

The first composition may be in the form of rice, porridge, gruel,congee, or cooked rice. The starch component in these forms is lesslikely to degrade after steaming, boiling or other forms of cooking andtherefore less likely to elevate blood glucose level.

The second composition may be capable of reducing endotoxin-producingbacteria population in a subject. In one embodiment, the secondcomposition may consist essentially of the bitter gourd, the firstfermentable dietary fiber, and the first oligosaccharides. The bittergourd may include powder of whole fruits from a plant of Momordicacharantia or its extract. The powder of fruits may be produced by freezedrying or spray drying process. The first fermentable dietary fiber mayinclude Fibersol-2, resistant starch, polydextrose, cellulose,hemicellulose, pectin, gum, or a combination thereof. The firstoligosaccharides may include independently fractooligosaccharides,galacto-oligosaccharides, lactulose, xylo Isomaltooligosaccharide,soybean oligosaccharides, oligo glucose, Stachyose, Lactosucrose, or acombination thereof.

In one embodiment, the second composition may include from about 15 toabout 99.8% of the bitter gourd by weight, from about 0.1 to about 51%of the first fermentable dietary fiber by weight, and from about 0.1 toabout 34% of the first oligosaccharide by weight. In one embodiment, theratio of the bitter gourd and oligosaccharides in the second compositionmay be from about 10:1 to about 1:1 by weight. In one embodiment, theamount of the bitter gourd may be from about 15 to about 55%, such asabout 15%, about 20%, about 30%, about 35%, about 40%, about 45%, about50%, or about 55%, of the second composition by weight. In oneembodiment, the amount of oligofructose may be from about 10 to about30%, such as about 10%, about 15%, about 20%, about 25%, or about 30%,of the second composition by weight. In one embodiment, the amount ofisomaltooligosaccharide may be from about 5 to about 25%, such as about5%, about 10%, about 15%, about 20%, or about 25%, of the secondcomposition by weight.

The second composition may be in granular or powder form. For example,the second composition may be a granular infusion and can be dissolvedor suspended in water. For example, the bitter gourd may be in the formof powder.

The ingredients in the compositions may be in the form of powder,granule, particles, noodle, sheets, crystalline, paste, or solution. Theingredient powder, such as bitter gourd, may be produced byfreeze-drying or spray drying. In one embodiment, the granularparticles, noodles, and sheets may be made by pulverizing a mixture ofthe ingredients into a particle or powdery mixture and forming theparticle or powdery mixture into granular particles, noodles, or sheets.In one embodiment, from at least about 1% to at least about 70% of thegranular particles in the composition has a diameter of 0.65 mm orabove.

The compositions in the present application may be used as foodproducts, healthcare products, or nutraceuticals, such as dietarysupplements. When ingested by a subject in effective amount, thecomposition may be capable of increasing a first gut microbiotapopulation containing a short-chain fatty acid (SCFA)-producingbacteria, decreasing a second gut microbiota population containing anendotoxin producing bacteria in the subject, or both.

The composition may be mixed with pharmaceutically acceptable carrier toform pharmaceutical compositions. “Pharmaceutically acceptable carriers”include solvents, dispersants, coatings, fillers, adhesives, bulkingagents, biologically active agents such as antibacterial or antifungalagents, and isotonic and delayed absorption agents, which are suitablefor drug delivery.

The composition may be formulated to be compatible with its intendedroute of administration. (See, for example, U.S. Pat. No. 6,756,196,which is incorporated herein in its entirety.) Examples of routes ofadministration include oral, sublingual, buccal, and rectaladministration, as well as parenteral administration. For instance, acomposition of the present application may be in the form of tablet,capsule, pill, bar, granule, powder, film, microcapsule, aerosol, gruel,congee, porridge, rice or cooked rice, spirit, tincture, tonic, liquidsuspension, or syrup. It is advantageous to formulate oral compositionsin dosage unit form for ease of administration and uniformity of dosage.“Dosage unit form,” as used herein, refers to physically discrete unitssuited as unitary dosages for the subject to be treated, each unitcontaining a predetermined quantity of active ingredients calculated toproduce the desired therapeutic effect in association with the requiredpharmaceutical carrier.

The composition of the present application can be used to promotebeneficial intestinal bacteria and inhibit opportunistic pathogens.Therefore, the application provides systems for nutritional interventionfor reducing bodyweight or improving metabolic syndrome in a subject.The system may include the above compositions and an instructionconfigured to instruct the subject on how to use the first composition,the second composition, and the third composition.

For example, an effective amount of the composition may be administeredto a subject in need thereof via a proper route such as those describedabove.

As used herein, a “subject” refers to a human or animal, including allmammals such as primates (particularly higher primates), sheep, dog,rodents (e.g., mouse or rat), guinea pig, goat, pig, cat, rabbit, andcow. In a preferred embodiment, the subject is a human. In anotherembodiment, the subject is an experimental animal or animal suitable asa disease model.

A subject to be treated may be identified in the judgment of the subjector a health care professional, and can be subjective (e.g., opinion) orobjective (e.g., measurable by a test or diagnostic method). Forexample, a subject to be treated may have a low level of beneficialintestinal bacteria and a high level of opportunistic pathogens, or hasbeen diagnosed with metabolic syndrome.

A “treatment” is defined as administration of a substance to a subjectwith the purpose to cure, alleviate, relieve, remedy, prevent, orameliorate a disorder, symptoms of the disorder, a disease statesecondary to the disorder, or predisposition toward the disorder.

An “effective amount” is an amount of a composition that is capable ofproducing a medically desirable result in a treated subject. Themedically desirable result may be objective (i.e., measurable by sometest or marker) or subjective (i.e., subject gives an indication of orfeels an effect).

The dosage required for treating a subject depends on the choice of theroute of administration, the nature of the formulation, the nature ofthe subject's illness, the subject's size, weight, surface area, age,gender, other drugs being administered, and/or the judgment of a healthcare professional.

The application further provides instructions for taking the abovecompositions. In one embodiment, the subject is instructed to take thefirst composition as a main course of food, take the second compositionfrom about 0.25 to about 1 hour before meal, and take the thirdcomposition from about 2 to about 5 hours before meal or with breakfast.

In one embodiment, the first composition may be in the form of aporridge, a gruel, or a congee, and used as food by a subject,optionally in combination with fresh vegetables. The intake amount ofthe first composition may be set to the extent where the subject nolonger feels hungry. The second composition may be in the form of agranular infusion. The granular infusion may be suspended or dissolvedin warm water and consumer by a subject. The daily intake amount of thesecond composition may be from about 5 to about 100 grams, from about 30to about 80 grams, or from about 40 to about 60 grams. For example, thesubject may be instructed to take 2-3 bags at 20 g/bag per day dosage ofthe second composition with warm water. The third composition may alsobe a granular infusion. The daily intake amount of the third compositionmay be from about 5 to about 200 grams, from about 30 to about 100grams, or from about 50 to about 150 grams. The third composition may besuspended or dissolved in from about 300 to about 1500 ml or from about800 to about 1200 ml of water and then consumed by a subject with anempty stomach in the morning.

The representative administration cycle of the composition of thepresent application is from one week to several months, such as oneweek, two weeks, one month, two months, four months or eight months.When the level of beneficial gut microbiota in the subject's body beginsto rise and the level of opportunistic pathogens begins to decline, thedosage of the composition may be reduced gradually. When the compositionof the gut microbiota is restored to normal, the administration may beterminated.

The following examples are for illustration of the present application.The embodiments were implemented under the premise of the technicalsolution of the present application. The detailed implementation methodsand specific operation processes are provided. These examples are notintended to limit the scope of the application.

EXAMPLE 1 Effective Treatment of an Obese Volunteer by an ExampleComposition

The composition embodying the present application in a granular infusionform was administered to a volunteer with Body Mass Index (BMI) of 58.78on a daily basis for 24 weeks. The physiological and biochemicalindicators of the body and the changes in the gut microbiota during theadministration were systematically monitored. At the end of theintervention, the opportunistic pathogens in the intestine declined; thebeneficial bacteria in the intestine increased; intestinal endotoxinsentering the host's circulatory system were reduced, the inflammatoryresponse level in the volunteer was lowered; each and every parameter ofthe metabolic syndrome of the volunteer was significantly improved; andBMI was dropped to 41.50.

(1) The physical conditions of the volunteer before intervention

The volunteer was a 26-year-old male, having a height of 172.5 cm, aweight of 174.9 kg, a BMI of 58.78, and a waistline of 156.1 cm.According to the BMI evaluation criteria for Asian adults, thisvolunteer was a severely obese patient. After a systematic physicalexamination, this volunteer was diagnosed with severe metabolicsyndrome. His physiological and biochemical indicators are shown inTable 1 below.

(2) The composition used for intervention and treatment of the patient

For intervention and treatment of the patient, a granular infusion formof an example composition was used. The example composition has thefollowing formula: the amount of bitter gourd powder was 35%, the amountof wolfberry powder was 15%, the amount of soy protein powder was 10%,the amount of oligofructose was 20%, the amount ofisomaltooligosaccharide was 15%, and the amount of wheat fiber was 5%.This composition had good inhibitory effects for intestinalopportunistic pathogens, and was capable of specifically conditioningthe contents of the intestinal flora, as demonstrated by the resultsobtained.

The granular infusion was taken orally 2-3 bags per day (20 g/bag),after dissolving in warm water.

(3) Use of other intervention food

A. Food-like Composition No. 1. The Food-like Composition No. 1 is anexample composition in porridge form. The composition has theingredients including adlay, oat, buckwheat, white bean, yellow corn,red bean, soybean, yam, big jujube, peanut, lotus seed, and wolfberry.This food-like composition was a whole-grain product, with balancedprotein, carbohydrates and fat. It was rich in dietary fiber. It wascapable of supplementing the dietary and nutritional need of human bodysuch as vitamins and minerals.

The patient consumed the Food Composition No. 1 as staple food, togetherwith a suitable amount of fresh vegetables during each meal. The foodintake was not restricted, and the patient was at liberty to consume thefood until he no long felt hungry.

B. Food-like Composition No. 3: The Food-like Composition No. 3 is anexample composition in granular infusion form. The composition has theingredients including oligomeric factor and fermentable dietary fiber.This food-like composition was capable of clearing the intestinal tract,excluding stool, promoting beneficial intestinal bacteria, increasingthe production of gas by the beneficial intestinal bacteria, speeding upintestinal motility and emptying, and removing pathogenic bacteria andendotoxin producing bacteria.

This food-like composition contained 30-100 grams of oligosaccharides.The patient consumed this food-like composition every morning prior toother food, along with 800-1200 ml of water.

(4) Evaluation of the changes in the physiological and biochemicalindicators of the body and the effects of the intervention

TABLE 1 show the physiological and biochemical indicators of thevolunteer in example I after 9 weeks and 23 Weeks of Intervention

TABLE 1 Measurements 0 days 9 weeks 23 weeks before after after NormalItem intervention intervention intervention range Weight (kg) 174.9144.8 123.5 — BMI 58.78 48.66 41.50 18-23 fasting blood glucose-FBG 8.954.76 5.40 3.90-6.10 (mmol/L) fasting insulin FINS 58.7 25.8 23  6-27(μIU/ml) glycated hemoglobin (%) 7.58 5.44 4.52 3.8-5.8 insulinresistance 23.35 5.46 5.52 indicators triglycerides (mmol/L) 2.68 1.721.18  0-1.7 total cholesterol (mmol/L) 5.53 4.64 4.78 3.00-5.17 highdensity lipoprotein - 0.89 0.70 0.82    >0.91 HDL (mmol/L) low-densitylipoprotein- 3.42 3.15 3.42   0-4.16 LDL (mmol/L) AST (U/L) 122.0 51 3110-47 alanine aminotransferase 97.0 50 33  0-41 (U/L) gamma glutamyl168.0 49 59  0-56 transferase (U/L) fatty liver disease-FLD SevereSevere Moderate Normal systolic pressure-SBP 150.0 120 120 ≦140 (mmHg)diastolic pressure-DBP 110.0 80 75  ≦90 (mmHg) C reactive protein (mg/L)14.1 9.4 9.51  0-10 lipopolysaccharide 7.03 2.29 4.78 —endotoxin-binding protein (μg/ml) interleukin 1β (pg/ml) 0.12 0.14 0.09— interleukin 6 (pg/ml) 6.71 4.46 2.76 — tumor necrosis factor 1.10 2.141.66 — alpha, TNF (pg/ml) adiponectin (μg/ml) 2.00 2.09 4.27 —

A. The intervention by the composition of the present applicationsignificantly reduced BMI and drastically improved the metabolicsyndrome. Compared with the volunteer's physiological and biochemicalindicators 0 day before the intervention, after 9 weeks and 23 weeks ofintervention, the volunteer's weight and BMI dropped significantly; thedecrease in the indicators of fasting glucose, fasting insulin, glycatedhemoglobin, and insulin resistance directly reflects the significantimprovement of the state of glucose homeostasis under the intervention;the decline in triglycerides and total cholesterol indicates theimprovement of the body's lipid metabolism; the significant reductionand gradual return to the normal range of aspartate aminotransferase,alanine aminotransferase and γ-glutamyl transferase indicate themitigation of the liver cell damage; at the same time, both the symptomsof fatty liver disease and the blood pressure were relieved; thedecrease of both the inflammatory indicator C-reactive protein and theinflammatory factor interleukin-6 suggests that the level of theinflammatory response caused by the gut microbiota population and havinga destructive effect to the human body was reduced under theintervention; the increase of the anti-inflammatory factor adiponectinindicates that the function of the body to eliminate inflammatoryresponse recovered after the intervention; the decrease of thelipopolysaccharide endotoxin binding protein suggests that the level ofthe endotoxin produced by the bacteria and entering the blood wasreduced under the intervention. Taken together, these indicators allshow that, after the intervention in the volunteer, each parameter ofthe metabolic syndrome of the volunteer was significantly improved.

B. The intervention by the composition of the present applicationsignificantly changed the composition of the intestinal flora,increasing beneficial bacteria and decreasing harmful bacteria. Thechanges of the composition of the gut microbiota during the interventionwere measured by 16S rRNA gene V3-DGGE fingerprint. As shown in FIG. 1,the 16S rRNA gene V3-DGGE fingerprint shows that the dietaryintervention exerted a great impact on the composition of the gutmicrobiota in this individual. At several points after the intervention,the gut microbiota of the volunteer was relatively similar, indicatingthat the dietary intervention significantly changed the composition ofthe intestinal flora.

C. The results of 454 pyrosequencing reveal a significant decrease inProteobacteria in the volunteer. In particular, the change inEnterobacteriaceae was the most prominent, from 17.90% at −30 d to 0.10%at 9 w and 0.10% at 23 w. Reflected at the genus level, it wasmanifested by the significant decline of the opportunistic pathogenEnterobacter. In addition, at the genus level, after the dietaryintervention, the Faecalibacterium went upward. Faecalibacterium isanti-inflammatory and produces butyrate. It plays an important role inenergy metabolism in a host and the protection of the integrity of theintestinal mucosa.

Thus, after the intervention, the number of the opportunistic pathogensin the volunteer declined. The intestinal endotoxins entering the host'scirculatory system were reduced, the inflammatory response level in thehost was lowered, and the symptoms of metabolic syndrome in thevolunteer were effectively relieved.

EXAMPLE 2 Effective Treatment of 89 Obese Volunteers by an ExampleComposition

The same example composition and the intervention regime as described inEXAMPLE 1 was applied to 89 volunteers who suffered from second degreecentral obesity. The physiological and biochemical indicators and thechanges in the gut microbiota during the intervention weresystematically monitored for all 89 volunteers. After administering thecomposition in a granular infusion form on a daily basis for 24 weeks,the opportunistic pathogens in the intestine declined; the beneficialbacteria in the intestine increased; intestinal endotoxins entering thehost's circulatory system were reduced, the inflammatory response levelin the volunteer was lowered significantly; each and every parameter ofthe metabolic syndrome of the volunteer was significantly improved; andBMI were significantly reduced.

(1) The physical conditions of the volunteer before intervention

89 volunteers suffering from second degree central obesity wererecruited for the application.

(2) The composition used for intervention and treatment of the patient

The same composition as EXAMPLE 1 was used.

(3) Use of other intervention food-like composition

The same composition as EXAMPLE 1 was used.

(4) Evaluation of the changes in the physiological and biochemicalindicators of the body and the effects of the intervention

The data shown in TABLE 2 below are mean value±standard deviation, ormedian (interquartile range). Paired t test (normally distributed data)or nonparametric Wilcoxon test distribution (non-normally distributeddata) were analyzed by SPSS 17.0 statistical software. For comparisonbetween week 9 versus −30 days, and week 23 versus −30 days, * denotesP<0.05, ** denotes P<0.01; for comparison between week 9 versus week 23,§ denotes P<0.05, §§ denotes P<0.01.

TABLE 2 The physiological and biochemical indicators of the volunteersin EXAMPLE 2 during the process of dietary intervention Measurements 30days 9 weeks 23 weeks before after after Normal Item interventionintervention intervention range Weight (kg) 84.1  78.8**  78.25**^(§) —(76.7-92.1) (71.6-87.6) (72-87.7) BMI 31.51  29.81**  29.50**^(§) 18-23(30.31-33.91) (28.73-32.24) (28.43-31.47) FBG (mmol/L) 4.90 4.74**4.93^(§§ ) 3.90-6.10 (4.64-5.28) (4.46-5.13) (4.63-5.37) FINS (μIU/ml)11.9  10.7**    9.26**^(§§)  6-27  (8.5-17.1)  (6.9-14.3)  (6.10-13.95)Glycated hemoglobin 4.34 4.83**  4.78** 3.8-5.8 (%) (3.99-4.60)(4.63-5.06) (4.57-5.02) Insulin resistance 2.63 2.40**  1.96**^(§)indicators (1.80-3.92) (1.47-3.15) (1.27-3.10) Triglycerides 1.55 1.17** 1.29**  0-1.7 (mmol/L) (1.09-2.25) (0.86-1.80) (0.79-1.88) Totalcholesterol 4.45 ± 0.77 4.13 ± 0.77** 4.38 ± 0.78^(§§) 3.00-5.17(mmol/L) HDL (mmol/L) 1.05 ± 0.19 0.98 ± 0.21**  1.09 ± 0.23*^(§§)   >0.91 LDL (mmol/L) 2.46 ± 0.87 2.47 ± 0.76   2.61 ± 0.70*^(§)  0-4.16 AST (U/L) 21    21     22     10-47 (16-29) (17-27) (19-25)Alanine amino- 21    19**    17**     0-41 transferase (U/L) (13-36)(13-28) (10.5-26)   gamma glutamyl 27    22**    22**     0-56transferase (U/L) (20-36) (18-32) (16-31) SBP (mmHg) 127    123**   125     ≦140 (121-135) (116-131) (115-133) DBP (mmHg) 89    84*   89      ≦90 (80-97) (79-95) (80-95) C reactive protein 6.60 4.90**5.93*^(§)  0-10 (mg/L, n = 67) (5.10-8.20) (4.20-6.20) (4.69-6.85)lipopolysaccharide 23.21  19.98**  23.09^(§§ )  — endotoxin-binding(15.54-35.50) (14.15-30.83) (11.37-37.06) protein (μg/ml) Interleukin 1β(pg/ml) 0.07 0.07  0.06   — (0.03-0.12) (0.05-0.15) (0.03-0.13)Interleukin 6 (pg/ml) 2.28 2.02*    1.69**^(§§) — (1.79-3.12)(1.62-2.62) (1.27-2.47) Tumor necrosis factor 1.07 1.03  1.03*  — α(pg/ml) (0.87-1.49) (0.81-1.40) (0.80-1.54) adiponectin (μg/ml) 3.573.82**  4.20**^(§) — (2.56-5.22) (2.90-5.90) (3.00-6.20) intestinalpermeability  0.026  0.022**  0.023* — (0.020-0.031) (0.019-0.026)(0.019-0.026) Note: For the intestinal permeability test, 89 sampleswere collected 30 days prior to the intervention and 9 weeks after theintervention. 76 samples were collected 23 weeks after the intervention.

A. Compared with the volunteers' physiological and biochemicalindicators 30 days prior to the intervention, 9 weeks and 23 weeks afterthe intervention, the volunteers' body weight and BMI continuouslydropped significantly; the decrease in the indicators of fastingglucose, fasting insulin, glycated hemoglobin, and insulin resistancedirectly reflects the improvement of glucose homeostasis under theintervention; the decline in triglycerides and total cholesterolindicates the improvement of the body's lipid metabolism; thesignificant reduction of aspartate aminotransferase, alanineaminotransferase and γ-glutamyl transferase indicates the mitigation ofthe liver cell damage; at the same time, both the fatty liver disease(68.5% of the volunteers' conditions improved under the intervention,among which 18.0% returned to normal) and blood pressure were relieved;the decrease of both the inflammatory indicator C-reactive protein andthe inflammatory factors interleukin 6 and tumor necrosis factor −αsuggests that the level of the inflammatory response caused by the gutmicrobiota was reduced under the intervention; the increase of theanti-inflammatory factor adiponectin indicates that the function of thebody to eliminate inflammatory response recovered after theintervention; the decrease of the lipopolysaccharide endotoxin bindingprotein suggests that the level of the endotoxin produced by thebacteria and entering the blood was reduced under the intervention.

B. The intervention by the composition of the present applicationsignificantly changed the composition of the intestinal flora. Theresults of 454 pyrosequencing show that the number of Proteobacteria inthe volunteers decreased significantly while the number of Actinomycetesincreased significantly after the intervention. Primarily, threefamilies showed obvious changes after the dietary intervention. Thenumbers of Enterobacteriaceae and Desulfovibrio dropped significantly,while the number of Bifidobacteria increased significantly.

After the intervention, the numbers of two types of common pathogens,Enterobacteriaceae and Desulfovibrio, in the volunteers declinedsignificantly, while the number of Bifidobacteria, which can protect theintestinal barrier, increased significantly. The intestinal permeabilitywas lowered, and the intestinal endotoxins entering the host'scirculatory system were reduced, resulting in the decrease of theinflammatory response level in the host and relief of the symptoms ofmetabolic syndrome.

From the foregoing it will be appreciated that, although specificembodiments of the application have been described herein for purposesof illustration, various modifications may be made without deviatingfrom the spirit and scope of the application. Accordingly, theapplication is not limited except as by the appended claims.

With respect to the use of substantially any plural and/or singularterms herein, those having skill in the art can translate from theplural to the singular and/or from the singular to the plural as isappropriate to the context and/or application. The varioussingular/plural permutations may be expressly set forth herein for sakeof clarity.

It will be understood by those within the art that, in general, termsused herein, and especially in the appended claims (e.g., bodies of theappended claims) are generally intended as “open” terms (e.g., the term“including” should be interpreted as “including but not limited to,” theterm “having” should be interpreted as “having at least,” the term“includes” should be interpreted as “includes but is not limited to,”etc.). It will be further understood by those within the art that if aspecific number of an introduced claim recitation is intended, such anintent will be explicitly recited in the claim, and in the absence ofsuch recitation no such intent is present. For example, as an aid tounderstanding, the following appended claims may contain usage of theintroductory phrases “at least one” and “one or more” to introduce claimrecitations. However, the use of such phrases should not be construed toimply that the introduction of a claim recitation by the indefinitearticles “a” or “an” limits any particular claim containing suchintroduced claim recitation to embodiments containing only one suchrecitation, even when the same claim includes the introductory phrases“one or more” or “at least one” and indefinite articles such as “a” or“an” (e.g., “a” and/or “an” should be interpreted to mean “at least one”or “one or more”); the same holds true for the use of definite articlesused to introduce claim recitations. In addition, even if a specificnumber of an introduced claim recitation is explicitly recited, thoseskilled in the art will recognize that such recitation should beinterpreted to mean at least the recited number (e.g., the barerecitation of “two recitations,” without other modifiers, means at leasttwo recitations, or two or more recitations).

Furthermore, in those instances where a convention analogous to “atleast one of A, B, and C, etc.” is used, in general such a constructionis intended in the sense one having skill in the art would understandthe convention (e.g., “a system having at least one of A, B, and C”would include but not be limited to systems that have A alone, B alone,C alone, A and B together, A and C together, B and C together, and/or A,B, and C together, etc.). It will be further understood by those withinthe art that virtually any disjunctive word and/or phrase presenting twoor more alternative terms, whether in the description, claims, ordrawings, should be understood to contemplate the possibilities ofincluding one of the terms, either of the terms, or both terms. Forexample, the phrase “A or B” will be understood to include thepossibilities of “A” or “B” or “A and B.”

In addition, where features or aspects of the disclosure are describedin terms of Markush groups, those skilled in the art will recognize thatthe disclosure is also thereby described in terms of any individualmember or subgroup of members of the Markush group. As will beunderstood by one skilled in the art, for any and all purposes, such asin terms of providing a written description, all ranges disclosed hereinalso encompass any and all possible sub-ranges and combinations ofsub-ranges thereof. Any listed range can be easily recognized assufficiently describing and enabling the same range being broken downinto at least equal halves, thirds, quarters, fifths, tenths, etc. As anon-limiting example, each range discussed herein can be readily brokendown into a lower third, middle third and upper third, etc. As will alsobe understood by one skilled in the art all language such as “up to,”“at least,” “greater than,” “less than,” and the like include the numberrecited and refer to ranges which can be subsequently broken down intosub-ranges as discussed above. Finally, as will be understood by oneskilled in the art, a range includes each individual member. Forexample, a group having 1-3 cells refers to groups having 1, 2, or 3cells. Similarly, a group having 1-5 cells refers to groups having 1, 2,3, 4, or 5 cells, and so forth. While various aspects and embodimentshave been disclosed herein, other aspects and embodiments will beapparent to those skilled in the art.

The various aspects and embodiments disclosed herein are for purposes ofillustration and are not intended to be limiting, with the true scopeand spirit being indicated by the following claims.

1. A composition comprising: a first composition; a second composition;and a third composition, wherein: the first composition comprises atleast one of whole cereals, beans, nuts, cloves, star anise, fennel,thistle, yam, hawthorn, purslane, Zaocys dhumnades, plum, papaya, hempseed, odoratum, fragrant Solomonseal rhizome, licorice, angelica,ginkgo, white lentils flower, longan pulp, cassia, lily, nutmeg,cinnamon, amla, bergamot, Hippophae rhamnoides, oysters, Gorgon fruit,pepper, red beans, donkey hide gelatin, inner wall of chicken gizzard,malt, kelp, jujube, Momordica grosvenori, Yu Li seed, honeysuckleflower, olive, Houttuynia cordata, ginger, Hovenia dulcis Thunb, medlar,gardenia, Amomum villosum, Pang Dahai, Poria, citron, Elsholtzia, peachkernel, mulberry leaf, mulberry, orange, bellflower, Alpinia oxyphylla,lotus leaf, semen raphani, lotus seed, Alpinia officinarum hance,Lophatherum gracile, fermented soybean, chrysanthemum, chicory, HuangJiezi, Huang Jing, perilla seed, perilla seed, Ge Gen, black sesameseed, black pepper, Sophora japonica, sophora flower, dandelion, honey,Torreya, semen Ziziphi Spinosae, fresh Rhizoma imperatae, fresh reedrhizome, viper, orange peel, coix seed, peppermint, Allium macrostemonBunge, raspberry, or ageratum, the second composition comprises at leastone of bitter gourd, a first fermentable dietary fiber, or a firstoligosaccharide, and the third composition comprises a secondfermentable dietary fiber and a second oligosaccharide.
 2. Thecomposition of claim 1, wherein the whole cereals comprises at least oneof wheat, barley, quinoa, millet, rye, triticale, buckwheat, oat, orcorn, wherein the beans comprise at least one of soybeans, black beans,broad beans, white beans, peas, mung bean, long bean, Pigeonpea, fourwinged bean, chickpea, lentil, red beans, Pinto bean, green bean, kidneybean, Navy bean, Pea bean, Lima bean, black bean, Garbanzo peas,black-eyed peas, lablab bean, white lentils, or red bean, wherein thenuts comprises at least one of peach seeds, almonds, gingko seeds, prpeanuts, and wherein the jujube comprises at least one of Zizyphusjujube, sour jujube, black jujube, or common jujube. 3.-13. (canceled)14. The composition of claim 1, wherein the first composition comprises,per 100 g, Vitamin A from about 3 to about 857 μgRE, Vitamin D fromabout 0.01 to about 5 μgRE, Vitamin E from about 2 to about 79.09 mg,Vitamin B₁ from about 0.01 to about 1.89 mg, Vitamin B2 from about 0.01mg to about 1.4 mg, Vitamin B₆ from about 0.01 to about 1.2 mg, VitaminB₁₂ from about 0.1 to about 2.4 mg, Vitamin C from about 1 mg to about1170 mg, Niacin from about 0.5 mgNE to about 28.4 mg, Ca from about60-2458 mg, P from about 200 to about 1893 mg, K from about 350 to about1796 mg, Na from about 8 to about 2200 mg, Mg from about 100 to about350 mg, and Fe from about 2 to about 20 mg. 15.-17. (canceled)
 18. Thecomposition of claim 17, wherein the whole cereals comprises wholecereals particles, and wherein at least about 25% of the whole cerealparticles have a diameter of at least 0.65 mm.
 19. The composition ofclaim 1, wherein the first composition is capable of increasingshort-chain fatty acid (SCFA)-producing bacteria population in asubject.
 20. The composition of claim 1, wherein the second compositionconsists essentially of the bitter gourd, the first fermentable dietaryfiber, and the first oligosaccharides. 21.-23. (canceled)
 24. Thecomposition of claim 1, wherein the first or the second fermentabledietary fiber comprises at least one of Fibersol-2, resistant starch,polydextrose, cellulose, hemicellulose, pectin, or gum, respectively.25. The composition of claim 1, wherein the first or the secondoligosaccharides comprises at least one of fructooligosaccharides,galacto-oligosaccharides, lactulose, xylo isomaltooligosaccharide,soybean oligosaccharides, oligo glucose, Stachyose, or Lactosucrose,respectively.
 26. The composition of claim 1, wherein the secondcomposition comprises the bitter gourd in about 15% to about 99.8% byweight, the first fermentable dietary fiber in an amount from about 0.1%to about 51% by weight, and the first oligosaccharide in an amount fromabout 0.1% to about 34% by weight.
 27. (canceled)
 28. The composition ofclaim 1, wherein the second composition is capable of reducing endocrinetoxin-producing bacteria population in a subject.
 29. A nutritionalintervention composition comprising: a first composition; a secondcomposition; and a third composition, wherein: the first compositioncomprises an ingredient from an edible plant, the second compositioncomprises at least one of bitter gourd, a first fermentable dietaryfiber, or a first oligosaccharide, and the third composition comprises asecond fermentable dietary fiber or a second oligosaccharide, or acombination thereof.
 30. The nutritional intervention composition ofclaim 29, wherein the first composition comprises adlay, oat, andbuckwheat.
 31. The nutritional intervention composition of claim 29,wherein the first composition comprises white Hyacinth bean, yellowcorn, red bean, soybean, yam, peanut, lotus seed and wolfberry.
 32. Thenutritional intervention composition of claim 29, wherein the firstcomposition comprises protein from about 10% to about 20% by weight, fatfrom about 2% to about 15% by weight, carbohydrate from about 50% toabout 70% by weight, and fermentable dietary fibers from about 2% toabout 155 by weight.
 33. The nutritional intervention composition ofclaim 29, wherein, when ingested by a subject in effective amount, thenutritional intervention composition is capable of increasing a firstgut microbiota population or decreasing a second gut microbiotapopulation in the subject, wherein the first gut microbiota populationcomprises a short-chain fatty acid (SCFA)-producing bacteria, andwherein the second gut microbiota population comprises an endotoxinproducing bacteria.
 34. The nutritional intervention composition ofclaim 29, wherein, when ingested by a subject in effective amount, thefirst composition is capable of increasing a first gut microbiotapopulation, and the second composition is capable of decreasing a secondgut microbiota population in the subject, wherein the first gutmicrobiota population comprises a short-chain fatty acid(SCFA)-producing bacteria, and wherein the second gut microbiotapopulation comprises an endotoxin producing bacteria.
 35. (canceled) 36.A method for nutritional intervention in a subject, comprising providingthe subject a nutritional intervention composition comprising a firstcomposition, a second composition and a third composition, wherein: thefirst composition comprises an ingredient from an edible plant, thesecond composition comprises at least one of bitter gourd, a firstfermentable dietary fiber, or a first oligosaccharide, and the thirdcomposition comprises a second fermentable dietary fiber or a secondoligosaccharide, or a combination thereof; and providing the subjectwith the first composition as a main course of food, with the secondcomposition from about 0.25 to about 1 hour before a meal, and with thethird composition from about 2 to about 5 hours before the meal or alonewith a breakfast.
 37. The method of claim 36, wherein the firstcomposition comprises an ingredient from an edible plant, wherein thefirst composition is capable of increasing a first gut microbiotapopulation or decreasing a second gut microbiota population in thesubject after a period of time, wherein the first gut microbiotapopulation comprises a short-chain fatty acid (SCFA)-producing bacteria,and wherein the second gut microbiota population comprises an endotoxinproducing bacteria.
 38. The method of claim 36, wherein the secondcomposition is capable of increasing a first gut microbiota populationor decreasing a second gut microbiota population in the subject after aperiod of time, wherein the first gut microbiota population comprises ashort-chain fatty acid (SCFA)-producing bacteria, and wherein the secondgut microbiota population comprises an endotoxin producing bacteria. 39.The method of claim 36, wherein the third composition is capable ofaccelerating intestinal motility or emptying rate, wherein the thirdcomposition is capable of increasing a first gut microbiota populationor decreasing a second gut microbiota population in the subject after aperiod of time, wherein the first gut microbiota population comprises ashort-chain fatty acid (SCFA)-producing bacteria, and wherein the secondgut microbiota population comprises an endotoxin producing bacteria.